crossing96/oncoscreening huggingface dataset:
The biology and rationale of targeting nectin-4 in urothelial carcinoma.	Bladder cancer is the tenth most common cancer type worldwide. Urothelial carcinoma is the most common type of bladder cancer and accounts for 90% of bladder cancer cases in the USA and Europe. Novel approaches are needed to improve patient outcomes. Nectin-4 is a tumour-associated antigen found on the surface of most urothelial carcinoma cells. In the antibody-drug conjugate enfortumab vedotin, human anti-nectin-4 antibody is linked to the cytotoxic microtubule-disrupting agent monomethyl auristatin E. In ongoing phase I, II and III clinical trials, enfortumab vedotin has been evaluated as a monotherapy and in combination with a checkpoint inhibitor and/or chemotherapy in locally advanced and metastatic urothelial carcinoma. Encouraging data from the phase II study resulted in the FDA granting accelerated approval for enfortumab vedotin in December 2019 for patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum and a checkpoint inhibitor therapy. Moreover, data from a phase I study led to the FDA granting breakthrough therapy designation to enfortumab vedotin combined with pembrolizumab as a first-line treatment in February 2020 for cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma. Results of ongoing and future combination studies of enfortumab vedotin with immunotherapy and other novel agents are eagerly awaited.	bladder
Short-term mortality risks among patients with non-metastatic bladder cancer.	BACKGROUND: Population-based analysis for the short-term non-bladder cancer related mortality among patients with non-metastatic bladder cancer is currently lacking. The objective of the current study was to assess and quantify cause of death after bladder cancer diagnosis. METHODS: The custom Surveillance, Epidemiology, and End Results (SEER) dataset for standardized mortality ratios (SMRs) was utilized to identify 24,074 patients who were diagnosed with nonmetastatic (M0) bladder cancer from 2014 to 2015. SMRs for causes of death were calculated. Risk factors for bladder cancer-specific mortality, competing mortality, second-cancer mortality, and noncancer mortality were determined using either multivariable Cox or competing risk regression models. RESULTS: Among all the 4179 (17.4%) deaths occurred during the follow-up period, almost half of them (44.2%) were attributed to non-bladder cancer cause, including second non-bladder cancer (10%) and other non-cancer causes (34.2%). The most common noncancer causes of death were heart diseases followed by chronic obstructive pulmonary disease. Patients had a higher risk of death from second malignancies (SMR, 1.59; 95% CI, 1.47-1.74) compared with death from first malignancies in the US general population, and also had higher risks of death from heart diseases (SMR, 1.29; 95% CI, 1.18-1.40) and chronic obstructive pulmonary disease (SMR, 1.52; 95% CI, 1.29-1.79) compared with the US general population. Additionally, some risk factors for competing second malignancies or noncancer mortality were determined, such as age, gender, marital status and treatment modalities. CONCLUSIONS: Death from non-bladder cancer cause contributed to almost half of all deaths in bladder cancer survivors during the short-term follow-up period. These findings can inform medical management and assist clinicians in counseling those survivors regarding their short-term health risks.	bladder
The role of antibody expression and their association with bladder cancer recurrence: a single-centre prospective clinical-pilot study in 35 patients.	BACKGROUND: Bladder cancer (BC) is the 10th most common cancer in the UK, with about 10,000 new cases annually. About 75-85% of BC are non-muscle invasive (NMIBC), which is associated with high recurrence and progression rates (50-60% within 7-10 years). There are no routine biomarkers currently available for identifying BC patients at increased risk of developing recurrence. The focus of this research study was to evaluate antibody expression in BC patients and their association with cancer recurrence. METHODS: 35 patients scheduled for TURBT were recruited after written informed consent. Ethical approval for the project was granted via IRAS (REC4: 14/WA/0033). Following surgical procedure, tissues were preserved in 10% buffered formalin and processed within 24 h in FFPE blocks. 7 sections (4 µm each) were cut from each block and stained for CD31, Human epidermal growth factor receptor-2 (HER-2), S100P, Cyclooxygenase-2 (COX-2), VEGFR-3 thrombomodulin and CEACAM-1 using immunohistochemistry. Clinical outcome measures (obtained via cystoscopy) were monitored for up to 6 months following surgical procedure. RESULTS: There was significantly increased expression of CD31 (p < 0.001), HER-2 (p = 0.032), S100P (p < 0.001), COX-2 (p < 0.001), VEGFR-3 (p < 0.001) and decreased expression of thrombomodulin (p = 0.010) and CEACAM-1 (p < 0.001) in bladder tumours compared to normal bladder tissues. HER-2 expression was also significantly associated with cancer grade (p = 0.003), especially between grade 1 and grade 2 (p = 0.002) and between grade 1 and grade 3 (p = 0.004). There was also a significant association between cancer stage and HER-2 expression (p < 0.001). Although recurrence was significantly associated with cancer grade, there was no association with antibody expression. CONCLUSION: Findings from the present study may indicate an alternative approach in the monitoring and management of patients with BC. It is proposed that by allowing urological surgeons access to laboratory markers such as HER-2, Thrombomodulin and CD31 (biomarker profile), potentially, in the future, these biomarkers may be used in addition to, or in combination with, currently used scoring systems to predict cancer recurrence. However, verification and validation of these biomarkers are needed using larger cohorts.	bladder
Intraoperative Ureteral Stent Use at Radical Cystectomy is Associated with Higher 30-Day Complication Rates.	PURPOSE: Radical cystectomy/urinary diversion is a high risk procedure. Intraoperative stents are commonly utilized to decrease ureteroenteric anastomosis related complications. Institutionally some surgeons routinely use intraoperative stents while others do not, providing an opportunity to compare complication differences. MATERIALS AND METHODS: We queried a prospective database of 283 patients enrolled in a randomized controlled trial evaluating 30-day perioperative complications with goal directed fluid therapy following open radical cystectomy/urinary diversion between 2014 and 2018. Ureteroenteric anastomosis specific complications (ureteral obstruction, urinary leak, urinary infections/sepsis and intra-abdominal abscess) were compared between groups (intraoperative stent vs nonintraoperative stent group) using Fisher exact test and quantified using logistic regression. RESULTS: The nonintraoperative stent group (77 of 283 patients, 27%) was older (median 72 vs 69 years) and was more likely to receive neoadjuvant chemotherapy (53% vs 40%), have baseline renal insufficiency (43% vs 30%) and undergo an ileal conduit (92% vs 53%). However, despite higher comorbidity, the nonintraoperative stent group had a significantly lower rate of ureteroenteric anastomosis complications (14% vs 32%, p=0.004). Since continent diversions may be associated with higher complications, the nonintraoperative stent group with ileal conduit was also compared to intraoperative stent cohorts with ileal conduit, and ureteroenteric anastomosis complications remained lower in the nonintraoperative stent group (14% vs 28%, p=0.043). Multivariable logistic regression showed significantly increased odds of urinary complications with intraoperative stent use (OR 3.55, 95% CI 2.93-4.31; p <0.0001). Importantly there was no obstruction and only 1 leak (1.3%) in the nonintraoperative stent group. CONCLUSIONS: Contrary to conventional belief, we found intraoperative stent use in radical cystectomy/urinary diversion was associated with significantly higher infectious complications and urgent care visits, and significantly increased the odds of 30-day ureteroenteric anastomosis associated complications.	bladder
LncRNA MAFG-AS1 Promotes the Progression of Bladder Cancer by Targeting the miR-143-3p/COX-2 Axis.	BACKGROUND: Long noncoding RNAs (lncRNAs) are potential biomarkers that are very important for the development of cancer. Studies show that lncRNAs are significantly correlated with the carcinogenesis and progression of bladder cancer (BLCA). In this research, we aimed at probing into the role of lncRNA MAFG-AS1 in the tumorigenesis of BLCA. METHODS: RT-qPCR was employed to detect MAFG-AS1 expression in BLCA tissues and cells. MAFG-AS1 siRNA and overexpression plasmid were transfected into 5637 and T24 BLCA cell lines to inhibit or upregulate MAFG-AS1 expression, respectively, and then the regulatory functions of MAFG-AS1 on BLCA cell proliferation, migration, and invasion were assessed using cell counting kit-8 (CCK-8) assay, EdU method, and Transwell experiments, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation were conducted to validate the targeting relationships between MAFG-AS1 and miR-143-3p, and miR-143-3p and COX-2. In addition, miR-143-3p was repressed in MAFG-AS1-silenced 5637 and T24 cell lines, and the function of MAFG-AS1/miR-143-3p axis in BLCA cells was further evaluated. The regulatory effects of MAFG-AS1 and miR-143-3p on the expression of COX-2 protein were detected by Western blot. RESULTS: MAFG-AS1 was remarkably upregulated in BLCA patient tissues and cell lines, and its high expression was closely related to histological grade, tumor size, and lymph node metastasis. Silencing of MAFG-AS1 inhibited BLCA cell proliferation, metastasis, and invasion, while overexpression of MAFG-AS1 in BLCA cells had opposite biological effects. MAFG-AS1 was proved to target miR-143-3p to repress its expression. Moreover, it was confirmed that MAFG-AS1 and miR-143-3p could modulate COX-2 expression. CONCLUSION: The MAFG-AS1/miR-143-3p/COX-2 axis contributes to BLCA progression.	bladder
p-120 Catenin is a Useful Diagnostic Biomarker for Distinguishing Plasmacytoid and Sarcomatoid Variants From Conventional Urothelial Carcinoma.	CONTEXT.—: Plasmacytoid urothelial carcinoma (PC-UC) is an aggressive variant of urothelial carcinoma (UC), characterized by loss of E-cadherin (E-Cad)-mediated intercellular adhesion. Loss of E-Cad by immunohistochemistry can help diagnose PC-UC; however, sensitivity is limited. Expression of other cadherin-catenin adhesion complex members, that is, p-120 catenin (p-120) and β-catenin (B-Cat), which are diagnostically useful for lobular breast carcinoma, remains unknown in UC. OBJECTIVE.—: To determine the utility of p-120 and B-Cat in conventional and variant UC. DESIGN.—: E-cadherin, B-Cat, and p-120 immunohistochemistry was performed in 25 conventional UCs and 33 variant UCs, including 22 PC-UCs, 6 sarcomatoid UCs (SUCs), and 5 micropapillary UCs. Membranous staining for all biomarkers was considered normal; however, any cytoplasmic staining or an absence of staining was considered diagnostically abnormal. Next-generation sequencing was performed on 8 PC-UC cases. RESULTS.—: E-cadherin, B-Cat, and p-120 showed membranous staining in all conventional and micropapillary UCs. In contrast, most PC-UCs were negative for E-Cad (17 of 22; 77%) with an additional 2 of 22 cases (9%) showing cytoplasmic with partial membranous staining. p-120 catenin demonstrated cytoplasmic or negative staining in 21 of 22 cases (95%). Most SUCs showed an absence of E-Cad (5 of 6; 83%) and cytoplasmic or negative p-120 in 5 of 6 cases (83%). Staining for B-Cat was also abnormal in a subset of PC-UCs and SUCs. Five PC-UC cases that harbored CDH1 gene variants were p-120 cytoplasmic positive. CONCLUSIONS.—: p-120 catenin is a useful adjunct biomarker to E-Cad in the clinically important distinction of PC-UC and SUC from conventional UC. In particular, the combination of cytoplasmic p-120 and loss of E-Cad is strongly supportive of PC-UC and SUC.	bladder
Sarcomatoid carcinoma of the urinary bladder: analysis of five cases and literature review.	Sarcomatoid carcinomas of the bladder represent a tiny part of bladder tumors and are characterized by a high potential for malignancy. Very aggressive and affecting mainly men, these tumors present both a urothelial and sarcomatoid contingent. The treatment of these tumors is not well codified given the rarity of cases reported in the literature, however, it seems that the treatment is essentially based on radical cystectomy with extensive pelvic lymph node dissection. We report the experience of our departement in the management of this type of tumor in a series of five cases collected over a period of 8 years.	bladder
The long noncoding RNA LINC01140/miR-140-5p/FGF9 axis modulates bladder cancer cell aggressiveness and macrophage M2 polarization.	MIBC (muscle invasive bladder cancer) only accounts for only a minority of bladder cancers, however, the disease-specific and overall survival rates of patients with MIBC are low. Macrophage M2 polarization has been reported to be associated with poorer prognosis in bladder cancer. Through cancer bioinformatics and experimental analyses, FGF9 was found to be upregulated in MIBC tissues. FGF9 knockdown in T24 cells strongly suppressed the viability, migratory capacity, and invasive capacity of cells; culture with medium from FGF9 knockdown T24 cells (si-FGF9-CM) significantly inhibited macrophage M2 polarization, while promoting M1 polarization. The long noncoding RNA (lncRNA) LINC01140 was positively correlated with FGF9 and was significantly upregulated in MIBC tissues. LINC01140 knockdown inhibited the viability, migratory capacity and invasive capacity of T24 cells; culture in si-LINC01140-CM also inhibited macrophage M2 polarization, while promoting M1 polarization. LINC01140 targeted miR-140-5p, while miR-140-5p targeted FGF9 to form a lncRNA-miRNA-mRNA axis. The effects of miR-140-5p inhibition on bladder cancer aggressiveness and macrophage M2 polarization were opposite to those of LINC01140 or FGF9 knockdown; additionally, miR-140-5p inhibition partially reversed the effects of LINC01140 knockdown on FGF9 protein levels, bladder cancer phenotype, and macrophage M2 polarization. In conclusion, LINC01140, miR-140-5p, and FGF9 form a lncRNA-miRNA-mRNA axis that modulates the bladder cancer phenotype, affects macrophage M2 polarization through the tumor microenvironment, and in turn affects bladder cancer cell aggressiveness.	bladder
The development of a behaviour questionnaire for stoma self-management for persons with bladder cancer and an ileal conduit.	AIMS: To develop and preliminarily test the reliability and validity of a behaviour questionnaire for stoma self-management for patients with bladder cancer after radical cystectomy and ileal conduit. DESIGN: A psychometric instrument validation study conducted in two phases. METHODS: The initial version of behaviour questionnaire was developed based on guidelines for people living with a stoma. Five experts validated the content of the preliminary 29-item questionnaire. A cross-sectional survey was then conducted in Beijing for preliminary reliability and validity tests between 4 December 2017-28 April 2018. A total of 151 participants in the survey, 147 of whom completed the study and 16 completed a 2-week test-retest reliability test. RESULTS: The content validity indices were satisfied. A principal component analysis with direct oblimin rotation was performed. Sixteen items were retained, and three factors were identified, namely, pouching system change, emotional management, and role management. The 16-item questionnaire showed acceptable internal consistency and test-retest reliability. The mediational effect of self-management behaviour on the relationship between self-efficacy and stoma quality of life was confirmed via convergent validity testing. CONCLUSION: The behaviour questionnaire for stoma self-management appears to have adequate initial reliability and validity. More observational and interventional studies need to be conducted for further evaluation of its psychometric properties. IMPACT: This study developed a reliable instrument to measure self-management behaviours for persons living with a stoma after radical cystectomy and ileal conduit. The questionnaire has practical value for both healthcare providers and researchers working in this field. The 16-item questionnaire can be administered quickly in clinical practice. Based on the questionnaire and the elicited mediational model, psycho-education programs tailored to improve self-management should be designed, implemented, and re-inspected regarding their effectiveness for the target population in China.	bladder
Bladder cancer stage and mortality: urban vs. rural residency.	OBJECTIVE: Relative to urban populations, rural patients may have more limited access to care, which may undermine timely bladder cancer (BCa) diagnosis and even survival. METHODS: We tested the effect of residency status (rural areas [RA < 2500 inhabitants] vs. urban clusters [UC ≥ 2500 inhabitants] vs. urbanized areas [UA, ≥50,000 inhabitants]) on BCa stage at presentation, as well as on cancer-specific mortality (CSM) and other cause mortality (OCM), according to the US Census Bureau definition. Multivariate competing risks regression (CRR) models were fitted after matching of RA or UC with UA in stage-stratified analyses. RESULTS: Of 222,330 patients, 3496 (1.6%) resided in RA, 25,462 (11.5%) in UC and 193,372 (87%) in UA. Age, tumor stage, radical cystectomy rates or chemotherapy use were comparable between RA, UC and UA (all p > 0.05). At 10 years, RA was associated with highest OCM followed by UC and UA (30.9% vs. 27.7% vs. 25.6%, p < 0.01). Similarly, CSM was also marginally higher in RA or UC vs. UA (20.0% vs. 20.1% vs. 18.8%, p = 0.01). In stage-stratified, fully matched CRR analyses, increased OCM and CSM only applied to stage T1 BCa patients. CONCLUSION: We did not observe meaningful differences in access to treatment or stage distribution, according to residency status. However, RA and to a lesser extent UC residency status, were associated with higher OCM and marginally higher CSM in T1N0M0 patients. This observation should be further validated or refuted in additional epidemiological investigations.	bladder
Current Landscape and Future Directions on Bladder Sparing Approaches to Muscle-Invasive Bladder Cancer.	Although radical cystectomy is considered the gold standard approach for patients with muscle-invasive bladder cancer, tri-modal therapy (TMT) is a well-tolerated and efficacious alternative to radical cystectomy that is underutilized in inoperable patients and rarely offered to cystectomy candidates in the USA. Retrospective data suggest similar outcomes between radical cystectomy and TMT after adjusting for patient selection and other confounding factors. Nearly 70-80% of patients can keep their native bladder with favorable post-treatment quality of life metrics. Current trials are investigating novel combination strategies including immune checkpoint inhibition along with chemoradiation or radiation. Emerging techniques for improved patient selection and risk stratification include incorporating MP-MRI, and novel biomarkers such as inflammatory, stromal, and DNA damage response gene signatures may guide patient selection and expand the landscape of bladder preservation options available to patients in the future.	bladder
Delaying BCG immunotherapy onset after transurethral resection of non-muscle-invasive bladder cancer is associated with adverse survival outcomes.	PURPOSE: This study was carried out to assess whether a prolonged time between primary transurethral resection of non-muscle-invasive bladder cancer (TURB) and implementation of bacillus Calmette-Guerin (BCG) immunotherapy (time to BCG; TTBCG) is associated with adverse oncological survival in patients with T1 high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data on 429 patients from 13 tertiary care centers with primary T1HG NMIBC treated with reTURB and maintenance BCG between 2001 and 2019 were retrospectively reviewed. Change-point regression was applied following Muggeo's approach. The population was divided into subgroups according to TTBCG, whereas the recurrence-free survival (RFS) and progression-free survival (PFS) were estimated with log-rank tests. Additionally, Cox regression analyses were performed. Due to differences in baseline patient characteristics, propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. RESULTS: The median TTBCG was 95 days (interquartile range (IQR): 71-127). The change-point regression analysis revealed a gradually increasing risk of recurrence with growing TTBCG. The risk of tumor progression gradually increased until a TTBCG of approximately 18 weeks. When the study population was divided into two subgroups (time intervals: ≤ 101 and > 101 days), statistically significant differences were found for both RFS (p = 0.029) and PFS (p = 0.005). Furthermore, in patients with a viable tumor at reTURB, there were no differences in RFS and PFS. After both PSM and IPW, statistically significant differences were found for both RFS and PFS, with worse results for longer TTBCG. CONCLUSION: This study shows that delaying BCG immunotherapy after TURB of T1HG NMIBC is associated with an increased risk of tumor recurrence and progression.	bladder
"Comparison Of Recurrence Rate Between ""EN BLOC"" Resection Of Bladder Tumour And Conventional Technique For Non-Muscle Invasive Bladder Cancer."	BACKGROUND: Conventional transurethral resection of urinary bladder tumour (TURBT) using a wire loop diathermy violates the basic principle of oncological surgery, i.e. dissection through normal tissue. However, in the en bloc technique, the tumour is removed as a single specimen. We compared the quality of specimen and recurrence rate at three months (first check cystoscopy) in both the en bloc and conventional resection techniques. METHODS: The subject accrual was done from June 1st, 2017 till June 30th, 2019 at a tertiary care hospital. Patients with newly diagnosed bladder tumour, solitary or multiple ≤3 cm were included in the study. Patients with carcinoma in situ, prior TURBT, or muscle-invasive bladder cancer were excluded. Eighty-two patients were available for final analysis, 41 in each group. RESULTS: Mean age, gender ratio, tumour features (grade, stage, median number, and size) were comparable in the two groups. Median Operative time [interquartile range- (IQR)] was 30 (25-39.5) minutes in the en bloc group as compared to 45 (33-63.5) minutes in the conventional group (p < 0.001). The detrusor muscle was seen at the base of the primary tumour in all 41 (100%) en bloc cases as compared to 23 (56 %) cases in the conventional group (p<0.001). Overall recurrence at the first surveillance cystoscopy was 17%, with an insignificant difference between the groups. Recurrence at primary site was 19.5% in conventional TURBT compared to en bloc resection (n=1, 2.4%), (p = 0.013). CONCLUSIONS: En bloc resection decreases the recurrence rate at the primary site. En bloc TURBT is a safe technique, providing high-quality specimens for histopathological evaluation and reducing the need for the second TURBT.	bladder